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Biomedical subjects

N Niederle

Publications and source records attributed to N Niederle.

At least 73 records · Page 4Linked to original sources
PubMed1991

Etoposide in patients with previously untreated non-small-cell lung cancer: a phase I study.

In a phase I study, a range of doses of etoposide (200-370 mg/m2 given i.v. daily on 3 consecutive days) were evaluated for tolerance and response as first-line treatment in 26 patients with non-small-cell lung cancer. The dose-limiting toxicity was myelosuppression, especially leukopenia. At dose levels of 350 and 370 mg/m2 etoposide per day, leukopenia of WHO grade 4 occurred in two and one of seven patients, respectively. No thrombocytopenia of this degree was observed. Myelosuppression was quickly reversible and noncumulative. Apart from alopecia, nonhematologic organ toxicities above WHO grade 2 were not seen. Toxicity analysis suggests that the recommended dose of single-agent etoposide for phase II studies in untreated patients is 330-370 mg/m2 given i.v. daily for 3 days. At the dose levels tested, 6 (23%) major responses could be induced. All responses were seen at a starting dose of greater than 300 mg/m2 per day. The median duration of response was 4 months. The median survival for all patients was 8 months and that for responding patients was 15 months.

Aged↗
PubMed1991

Interferon alfa-2b in acute- and chronic-phase chronic myelogenous leukaemia: initial response and long-term results in 54 patients.

Fifty-four patients with Ph1-positive chronic myelogenous leukaemia (CML) (48 with chronic-phase and six acute-phase disease) were treated with interferon alfa-2b subcutaneously (s.c.). The starting dose was 4 million units (MU)/m2 body surface area daily. It was reduced in parallel with serially determined leucocyte counts, and minimal effective doses were given as maintenance after achieving remission. Haematological remissions were induced in 22 of the 48 patients (46%) with chronic-phase disease. Thirteen patients (27%) revealed partial haematological remission and another 13 no response to treatment. No complete remission could be induced, although minor or partial cytogenetic responses were seen in 16 patients (33%). Moreover, a bcr-abl reduction was detected on Southern blot analysis in two patients. In chronic-phase disease, results of treatment were influenced by elapsed time after diagnosis, extent of previous treatment and interferon dosage. No beneficial effects of interferon were detected in the six patients with acute-phase disease. Principal acute side effects were fever and flu-like symptoms at the beginning of the therapy, which usually subsided within 3-7 days. Chronic side effects, especially weakness and neuropathy, were less frequent but more severe and necessitated discontinuation of treatment in 10 patients. In summary, interferon alfa-2b seems to be an effective treatment in early chronic-phase CML. Long-term effects on the course of the disease, however, must be determined.

Adolescent↗
PubMed1991

Etoposide, ifosfamide, and methotrexate with or without bleomycin in refractory or recurrent lymphomas.

The prognosis of patients with refractory or relapsed malignant lymphoma is poor. To improve the outcome of such patients, a therapeutic regimen of VIM +/- B (etoposide/ifosfamide plus mesna/methotrexate/ with or without bleomycin) was administered. Of 47 patients treated, 15 had relapsed following complete remission (CR) after first-line chemotherapy, 28 had failed to achieve CR with first-line therapy, and four failed to respond to multiple salvage regimens. All patients had received extensive prior chemotherapy, and 36 had received combinations containing doxorubicin. Eight patients had low-grade non-Hodgkin's lymphoma (NHL), 28 had high-grade NHL, and 11 patients had Hodgkin's disease. Overall response rate was 87%, with 45% CR and 42% partial remission (PR). Median relapse-free interval was 8 months in patients with CR and 6 months in those with PR. Of patients with CR, 43% were predicted to be without relapse at 2 years and 31% at 5 years. Median survival time for all patients treated with 14 months-22 months for those with CR and 10 months for those with PR. Probability of survival at 2 years was 30% in all patients, 50% in patients with CR, and 15% in those with PR. VIM +/- B appears to be effective against refractory or recurrent lymphoma, resulting in response in a large number of patients and long-term survival and possible cure in a small but significant number. Results indicate that VIM +/- B is particularly effective in patients with high-grade NHL who have responded suboptimally to primary therapy.

Adolescent↗
PubMed1991

Ifosfamide, methotrexate and 5-fluorouracil for pretreated advanced breast cancer.

A total of 51 fully evaluable patients with advanced and intensively pretreated breast cancer were treated with a combination chemotherapy of ifosfamide plus mesna, methotrexate and 5-fluorouracil. All patients had received at least one series of combined chemotherapy, 30 patients had received more than one combination and 41 patients had had anthracyclines before. Metastatic lesions in more than one site were found in 42 patients, and 24 patients had metastatic liver lesions. Partial remission was achieved in 10 patients (20%) and no change in 16 patients (31%). Survival was almost identical in both groups of responding patients and significantly shorter in treatment failures. Response was favorable in patients without pretreatment with anthracyclines. Two patients who received this protocol directly after progression with cyclophosphamide, methotrexate and 5-fluorouracil (CMF protocol) responded with a partial remission. Median time to progression was 7 months for partial responders and 4.5 months for patients achieving a no-change status. Median survival was 8 months for all patients. Toxicity was tolerable. Leukocytopenia and thrombocytopenia were treatment-limiting parameters. Overall, this protocol is well tolerable and effective in breast cancer patients with advanced disease and in intensively pretreated patients.

Adult↗
PubMed1991

Treatment of metastatic carcinoid tumors and the carcinoid syndrome with recombinant interferon alpha.

Fourteen patients with metastatic carcinoid tumors were treated with recombinant interferon alpha-2b at a dosage of 3-4 x 10(6) IU s.c. daily or every second day. No objective tumor regression was observed. Six out of 8 patients with carcinoids of the ileum and the caecum showed stable disease lasting for a median of 25 months (range 4-57). In 3 out of 6 patients with carcinoids of rectum, lung and of unknown primary site, stable disease was observed lasting for 2-7 months. The remaining patients had progressive disease. Six out of 9 evaluable patients had a more than 50% reduction of urinary 24 h 5-hydroxyindoleacetic acid excretion lasting for a median of 4 months (range 2-11). Decrease of flushing was noticed in 3 out of 6 evaluable patients and decrease of diarrhea in 5 out of 9 evaluable patients. In 4 patients dose reduction was necessary due to confusion and fatigue.

Carcinoid Tumor↗
PubMed1991

Investigations on the subclinical and clinical nephrotoxicity of interferon alpha-2B in patients with myeloproliferative syndromes.

Since the introduction of interferon alpha-2b (IFN alpha-2b) into clinical oncology there have been several reports dealing with acute renal failure during therapy with this new type of anticancer drug. We investigated 58 patients (pts) with myeloproliferative syndromes (56 pts with chronic myelogenous leukemia, 2 pts with essential thrombocythemia) who were treated with 4 x 10(6) IU IFN alpha-2b each day subcutaneously. In order to assess the nephrotoxic potential we used the following noninvasive methods: 1. Analysis of the excretion of 4 urinary enzymes (LDH, LAP, GGT, NAG), 2. Determination of the excretion of protein, albumin, alpha-1-microglobulin immunoglobulin G (Ig G), 3. serum creatinine. The investigations were done every 2 weeks and took 70 weeks. We found an increase in the excretion of all 4 enzymes which remained stable during the whole observation period, protein excretion was pathological in about 20% of all pts and reached values of up to 9.07 g/L alpha-1-microglobulin was excreted in pathological amounts in about 20% of all pts during the whole observation period, albumin was found in pathological quantities in about 15% of all pts and Ig G was pathologically increased in the urine in about 10% of the pts. Serum creatinine rose in 5-10% of the pts up to 1.5 mg/dL. In conclusion, IFN alpha-2b is capable of inducing combined glomerular and tubular damage. Therefore, avoiding additional nephrotoxic insults is desirable.

Adolescent↗
PubMed1991

Breakpoint localization within the M-bcr and clinical course do not correlate in patients with chronic myelogenous leukemia undergoing alfa interferon therapy.

The breakpoint localization was analyzed in 61 patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia to compare the breakpoint localization and clinical course. All patients were treated with interferon alfa (IFN alpha) or IFN alpha plus IFN gamma at the time of the study. Thirty-three of the patients had been pretreated with other cytostatic drugs. Sixty-nine per cent of the breakpoints were located in the 5' region of the major breakpoint cluster region (M-bcr), 29% in the 3' part. There was no significant difference between these two groups with respect to response to IFN(s), clinical course or conversion to blast crisis, nor survival.

Chromosome Fragility↗
PubMed1990

[Cardiac side effects of 5-fluorouracil].

In four patients (a 54-year-old man and three women aged 57, 60 and 65 years, respectively) with colorectal carcinoma and no obvious cardiac abnormality anginal symptoms and ECG changes occurred during chemotherapy with 5-fluorouracil at a dose of 400 and 600 mg/m2. The ECG changes consisted of descending ST depressions with preterminally negative T waves, terminally negative T waves, ventricular extrasystoles and sinus tachycardia with intermittent atrial fibrillation. The signs first appeared between the second and fourth day of treatment; in two patients they improved with glyceryl trinitrate. A few days after 5-fluorouracil had last been administered all ECG changes had disappeared. The causes of cardiotoxicity of the drug remain unknown.

Aged↗
PubMed1990

Investigations on the acute and chronic nephrotoxicity of the new platinum analogue carboplatin.

In order to detect even subclinical hints of nephrotoxicity after application of carboplatin, sensitive non-invasive methods, e.g. determination of urinary enzyme (lactate dehydrogenase, leucine aminopeptidase, gamma-glutamyltransferase, N-acetyl-beta-glucosaminidase), glomerular and tubular protein excretion (albumin, alpha-1-microglobulin) and determination of the creatinine clearance, were used. Eighteen patients with small-cell lung cancer entered the study. All patients were treated with the three-drug combination chemotherapy: vincristine (1.5 mg i.v. on days 1, 8, 15, 22), etopside (escalating doses: 100-160 mg/m2 on days 1-3) and carboplatin (300 mg/m2 day 1). Investigations were made during the first, third and fifth treatment cycles. Deterioration of renal function occurred in 4 out of 18 patients in all three observed treatment courses. Abnormal amounts in the excretion of at least one of four urinary enzymes were found in 6 out of 18 patients during the first cycle and in 4 out of 8 patients during the third and fifth cycles. All patients with pathological enzymuria during the first treatment course also developed an increased enzymuria during cycles 3 and 5. Four patients developed pathological proteinuria during the first and 2 patients during the third and fifth cycles. These findings demonstrate that the new platinum analogue, carboplatin, is capable of inducing renal damage. In comparison with cisplatinum, the nephrotoxicity of this new analogue is reduced but not completely eliminated.

Aged↗
PubMed1990

Treatment of chronic myelogenous leukemia with interferons alpha and gamma.

A 23-year-old male patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) was treated with both IFN alpha and IFN gamma. Normalization of leukocyte counts was reached after 3 months of treatment. Southern blot analysis failed to detect the neoplastic cell clone after 19 months of therapy. Cytogenetically, complete suppression of Ph positive cells in the patient's bone marrow and blood was observed after 20 months and 25 months, respectively. This response was achieved with doses of IFN alpha and IFN gamma which were considerably lower than the dosage of IFN used in single agent therapy of CML.

Adult↗
PubMed1990

DNA-flow cytometry studies in blood and marrow cells from chronic myelogenous leukemia patients treated with interferon alpha-2b.

Cell cycle distribution in bone marrow and peripheral blood mononucleated cells was studied in patients with chronic myelogenous leukemia (CML) before and during treatment with interferon (IFN) alpha-2b. DNA-flow cytometry with ethidium bromide fluorescence was used. Highly significant differences between mononucleated cells from CML patients and normal controls were seen in peripheral blood but not in bone marrow specimens. Patients achieving hematologic remission during IFN treatment showed a cell cycle distribution in bone marrow cells and peripheral blood cells similar to normal controls.

Bone Marrow↗
PubMed1990

[Interdisciplinary concepts and long-term results after surgery of pulmonary metastases].

From January 1976 to December 1988, 338 patients with pulmonary metastases underwent 376 resections. For 26 patients with recurrent disease a second or repeated thoracotomy was necessary. The operative mortality was for isolated lesions under 1%, for multiple bilateral nodules 3.8%. A parenchymal saving resection was performed, except for metastases from colorectal carcinoma, who often involved the bronchopulmonary lymphatic nodules. In these cases (30%) a segmentectomy or lobectomy was indicated. The five-year survival rates was significantly favorable for patients with isolated lesions, specially for late uterine metastases (57%), late mammary metastases (45%) and head and neck metastases (60%). The adjuvant hormones substitution and chemotherapy for multiple uterine and mammary metastases leaded to favorable results (prolonged median survival of 18 months). The indication for resection of multiple ipsilateral or bilateral lesions from testicular cancer, soft tissue and osteogenic sarcomas were recommended only when there was no response or partial response to the chemotherapy. The five-year survival was 46%, 27% and 17% approximately. The disease-free interval, location of the pulmonary lesions and the stage of primary cancer had not influenced on post-thoracotomy survival. The metastatic route of primary cancer, caval or portal route, size and number of metastases and the tumor doubling time was significantly associated with postoperative survival.

Adolescent↗
PubMed1989

[Sequential induction chemotherapy and radiation treatment of inoperable small cell bronchial cancer. Results of a prospective randomized study].

To study the potential benefit of sequential chemotherapy in inoperable small cell lung cancer (SCLC), from 1982 to 1986 ninety-one patients with histologically proven and previously untreated SCLC (median age: 53 years; median Karnofsky status: 80%) were randomly assigned to an initial therapy with adriamycin (since 1984 epirubicin), cyclophosphamide, vincristine (ACO resp. EPICO) or etoposide/cisplatin (VP16/DDP). Treatment courses were repeated every 3 weeks for a total of less than or equal to 6 courses with a crossover after a maximum of 3 cycles of either regimen. Limited disease (LD) patients with bronchoscopical, computertomographical and (re-) mediastinoscopical complete remission (CR) randomly received either a thoracic irradiation with 40 Gy or observation only. Overall, 60 out of 85 evaluable patients achieved an objective remission. A CR was observed in 24/51 patients (47%) with limited disease, and in 8/34 patients (24%) with extensive disease. Both, ACO (EPICO) and VP16/DDP were equally effective as initial and second-line therapy. Moreover, after failure to the initial therapy an objective remission could be achieved in 13% of the patients following the alternative second line combination. In 28% of LD patients with an otherwise complete remission residual tumor was detected by (re-) mediastinoscopy. Median survival times were 14 (CR: 16) months in LD patients and 10 (CR: 15) months in ED patients. At present, median survival is significantly improved in irradiated versus non-irradiated LD patients (25 vs. 13 months, p less than 0.04). The remission rates and median survival times observed in this study are comparable to those of a historical control group treated with ACO plus radiotherapy alone.

Adult↗